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July 2, 2016

Clinical update on dementia

Easier access to diagnostic tests such as brain scans is required

In his latest Clinical Update, Gary Culliton looks at recent developments in the area of dementia and the role of primary care in managing the condition.

Focus is shifting to earlier diagnosis

Dementia is a progressive, incurable illness, the prevalence of which is expected to rise due to the ageing population. The diagnosis and management of dementia requires multidisciplinary input and involves non-pharmacological and pharmacological approaches. Early diagnosis of dementia enables identification of causes, the treatment of co-morbid conditions as well as access to services for patients and carers. In addition, pharmacological treatment can be initiated, when appropriate.

Research over the past three-to-four years suggests that GPs would welcome more training and support in the diagnosis of dementia, said consultant psychiatrist Dr Henry O’Connell, who specialises in the psychiatry of later life. Easier access to diagnostic tests such as brain scans is also required.

A number of brief cognitive screening measures are available. The most commonly used is the Mini-Mental State Examination (MMSE) — a well-established, 30-item (approx. 10 minutes) questionnaire. This samples various cognitive domains and is also used in primary care.

“It is an initial screening measure. If there are concerns raised by the results of the MMSE, the guidance is that further testing on the individual should be done,” said Dr O’Connell. It has specificity for dementia diagnosis.

The Montreal Cognitive Assessment (MoCA) is a brief screening tool for mild cognitive impairment. (Nasreddine Z et al, American Geriatric Society 2005; Coen R et al, Int J Geriatr Psychiatry 2011). It is more detailed than the MMSE.

There are currently no disease-modifying drugs available for the treatment of dementia. In terms of pharmacological management, there are two main approaches: acetylcholinesterase inhibitors (AChEIs) and memantine are authorised primarily for patients with AD. It is assumed that the mechanism of action of AChEIs relates to increased cholinergic transmission via inhibition of breakdown of acetylcholine (Scottish Intercollegiate Guidelines Network (SIGN), 2006).

Evidence has shown that the use of AChEIs (donepezil, rivastigmine and galantamine) are of benefit in the management of mild-to-moderate AD. However, there is insufficient evidence to differentiate between the AChEIs in terms of clinical effectiveness (NICE technology appraisal guidance 217).

There is some evidence suggesting that AChEIs may have a possible disease-modifying effect (International Journal of Geriatric Psychiatry, 2009). However, more data are required before this can be confirmed (Hort J et al, EFNS guidelines, European Journal of Neurology 2010). Patients who do not tolerate one AChEI may tolerate another AChEI (Hogan D et al, CMAJ 2008). AChEIs are widely used in Ireland throughout the course of dementia and depending on access to primary care and specialist services, said Dr O’Connell.

Rivastigmine administered transdermally may be associated with a lower incidence of side effects and this may improve compliance (Chan A et al, Drugs Aging 2008).

Evidence suggests that oral rivastigmine also improves cognition in patients with dementia with Parkinson’s disease (Maidment I, Fox C, Boustani M, Cochrane 2006).

Patients with mixed dementia should be managed according to the condition that is thought to be the predominant cause of their dementia. (NICE Clinical Guideline 42, 2006, amended March 2011).

“We have a lot of expertise in the use of acetylcholinesterase inhibitors and memantine,” said Dr O’Connell. Memantine is a non-competitive N-methyl-D-aspartate receptor antagonist (NMDA) (McKeage K, CNS Drugs 2009). The NMDA antagonists work via the glutamate system; the blocking of the NMDA channel modulates the effects of pathologically-elevated levels of the neurotransmitter glutamate that may lead to neuronal dysfunction. Evidence supports the use of memantine in moderate-to-severe AD (McKeage K, Drugs 2009; Puangthong U, Robin Hsiung GY, Neuropsychiatric Disease and Treatment 2009; McShane R, Areosa Sastre A, Minakaran N, Cochrane 2006).

A recent review concluded that memantine offered symptomatic benefits in cognitive, functional, global and behavioural outcomes in patients with moderate-to-severe AD, although the size of the benefit was uncertain (NICE, 2011).

Combination therapy
There is some evidence to suggest the combination of memantine with AChEIs may be beneficial for the management of AD (Ballard C et al, Lancet March 2, 2011; McKeage K, CNS Drugs 2009; Puangthong U, Robin Hsiung GY, Neuropsychiatric Disease and Treatment 2009; Lopez OL et al, J Neurol Neurosurg Psychiatry 2009; Atri A et al, Alzheimer’s Dis Assoc Disord 2008; Wilkinson D, Anderson HF, Dement Geriatr Cogn Disord 2007). However, further studies are required (Hort J et al, European Journal of Neurology 2010; NICE 2011; Porsteinsson A et al, Current Alzheimer Research 2008). “Memantine seems to help with some of the behavioural problems associated with severe dementia,” said Dr O’Connell. “It can reduce carer burden, typically in the more moderate-to-severe stages of dementia.”

Future therapy may well focus on immunotherapy, along with the destruction and removal of plaques and tangles from individuals’ brains. Dr O’Connell expressed a hope that within the next 10 years, disease-modifying drugs would emerge. “These might address some aspects of immunotherapy or the metabolism of amyloid,” he said. “An active research stream means there are a number of new disease-modifying options in the pipeline. Such new therapeutic agents — which are not currently available — could potentially have a curative effect.”

The really exciting area for the future is that of prevention, in Dr O’Connell’s view. “At the moment, when many people present with even mild cognitive problems to primary care or specialist services, they may often have quite extensive changes to their brain. The emphasis in future needs to be on prevention of dementia.” Lifestyle and general health factors that will improve people’s resistance need to be considered. These might prevent the development of the brain disease Mild Cognitive Impairment (MCI) and ultimately dementia.

Anti-psychotic drugs have a limited role in the treatment of severe Behavioural and Psychological Symptoms of Dementia (BPSD), Dr O’Connell said. “They need to be used with caution at low doses. They need to be reviewed and discontinued as soon as possible,” he added.

Trained clinicians are ‘key’ to treatment

It is estimated that there are 42,000 people with dementia in Ireland currently. The Dementia Services Information and Development Centre in St James’s Hospital has taken an initiative in terms of serving GPs and training healthcare professionals generally in dementia diagnosis and treatment. The ICGP also has a role in this area.

A research review of dementia was published in January to provide an evidence base and inform attempts to address the issue. The estimates of people with dementia were updated and projections were made of future numbers in this category.

“Timely diagnosis and access to memory clinics are needed in order to tackle dementia,” said Dr Maria Pierce of TCD’s Living with Dementia research programme. “Primary care  — both diagnosis and post-diagnostic supports and services — was examined in the review,” said Dr Pierce. “Our impression is that diagnosis is the exception, rather than the rule. The experience internationally is that dementia is a difficult condition to diagnose. Estimates show that only 40 per cent of people with dementia are diagnosed. Well-trained primary care and other healthcare professionals are key. There is an obvious lack of these.”

42,000 people live with dementia

Major increase
A TCD conference that accompanied the review’s launch in January was attended by experts from Britain, Norway and Australia.

A major increase in the number of people with dementia in this country is likely to occur after the year 2021, with the numbers growing to between 141,000 and 147,000 by 2041, the TCD review found. In line with the projected growth in the number of the ‘oldest-old’ population, the most marked increase in the numbers with dementia will be amongst people aged 85 years old and over. Currently, approximately 4,000 new cases of dementia arise in the general Irish population every year.

The report calculated that there are 26,104 people with dementia who are currently living at home in the community. Most of these have not had a formal diagnosis. Many are not aware that they have the disease and few are likely to be in contact with the health and social care system, Dr Pierce said.

There are an estimated 50,000 family carers in Ireland looking after someone with at least one of the six specified symptoms of dementia. For example, there are an estimated 25,000 carers looking after someone with marked forgetfulness on a regular or occasional basis, while 15,000 people are looking after someone with confusion to the point of it interfering with everyday life.

An estimated 14,266 people with dementia live in various public and private long-stay facilities across the country, including 537 people aged under 65 years. The report suggested that 63 per cent of all long-stay residents have dementia.

Younger people
The prevalence of younger people and people with Down syndrome and dementia were gauged in the TCD review. Regional variations were also considered. People with dementia do not have an automatic right to those services — which are, in any case, underdeveloped, fragmented and inequitable, the report found. There are a number of Local Health Offices areas that do not have proper day care services, let alone services specifically for people with dementia, said Dr Pierce.

“People may not be willing to come forward; there may be a fear of being labelled,” said Dr Pierce. “There is also typically a period of delay before a diagnosis is made — particularly if the condition is complex. Ireland fares very poorly in relation to community care services (day care, home help and home care packages, respite care).

Unlike in other countries, there is not legislation to underpin services.”

The development of community support services would be a major advance. “Case management models of care for people with dementia are needed,” said Dr Pierce. “Increased awareness about dementia in the community is required.”

The review also examined the economic and social costs of dementia; about two-thirds of people with dementia live in the community and much of the cost is borne by family members.